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World Journal of Clinical Cases 2024年第17期12卷 3253-3258页

作者： xue-mei han Yi-Mai Zhou Lu-Sha Cen Department of Ophthalmology The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou 310006Zhejiang ProvinceChina The First Clinical Medical College Zhejiang Chinese Medicine UniversityHangzhou 310053Zhejiang ProvinceChina

BACKGROUND In addition to the non-specific symptomatology of ocular rosacea,currently,there are no reliable diagnostic tests for the disease,which may lead to its misdiagnosis.Here,we report a case of ocular rosacea presenting with multiple recurrent chalazion on both eyelids.CASE SUMMARY A 63-year-old female patient presented with multiple chalazion and dry eyes in both eyes,with no facial erythema.Initial management done were application of steroid eye ointment on both eyelids,hot compresses,and eyelid margin cleaning;noting that there was no relief of symptoms.Surgical excision of the chalazion was done on both eyes,however,bilateral recurrence occurred post-operatively.The pathological studies showed infiltration of a small amount of fibrous tissue with many chronic inflammatory cells.Immunohistochemistry studies were positive for LL-37.Resolution of the chalazion occurred after oral administration of doxycycline and azithromycin.CONCLUSION Our findings show that ophthalmologists should recognize the ocular manifestations of skin diseases.

关键词： Ocular rosacea Rosacea Recurrent chalazion Bilateral chalazion Multiple chalazion Case report

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus

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World Journal of Diabetes 2024年第2期15卷 196-208页

作者： han Shi Yuan Yuan xue Li Yan-Fang Li Ling Fan xue-mei Yang Department of Infectious Diseases The First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina

BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poo

关键词： Type 2 diabetes Pulmonary tuberculosis Blood sugar Infection Risk factors

Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

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Protein & Cell 2024年第6期15卷 403-418页

作者： Song xue Yuru han Fan Wu Qiao Wang Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecurityShanghai Frontiers Science Center of Pathogenic Microorganisms and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles.Point mutations,particularly those within the receptor binding domain(RBD)of SARS-CoV-2 spike(S)protein,lead to the functional alteration in both receptor engagement and monoclonal antibody(mAb)recognition.Here,we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune evasion.Many single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding affinity.However,this weakened effect could be largely compensated by specific epistatic mutations,such as N501Y,thus maintaining the overall ACE2 affinity for the spike protein of all major variants.The predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two dimensions.Together,this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained,emphasizing the significance of comprehensive assessment of spike mutations.

关键词： ACE2 affinity maintained

Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study

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World Journal of Hepatology 2024年第1期16卷 41-53页

作者： xue-mei Tao Ming-Hui Zeng You-Fei Zhao Jia-Xin han Yu-Qiang Mi Liang Xu Clinical School of the Second People’s Hospital Tianjin Medical UniversityTianjin 300192China Department of Hepatology Tianjin Second People’s HospitalTianjin 300192China Department of Hepatology Tianjin Research Institute of Liver DiseasesTianjin 300192China

BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce the occurrence of hepatocellular carcinoma(HCC)in patients with HCV-associated cirrhosis who are at high risk have not been concluded.AIM To investigate the effect of DAAs on the occurrence of HCC in patients with HCVassociated cirrhosis after achieving SVR.METHODS Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020.118 patients weren’t received antiviral treatment with any reasons named non-antiviral treatment group,and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group.Demographic information and laboratory data were collected from baseline and the following up.Kaplan-meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups.Cox proportional risk regression was used to re-evaluate the risk factors for HCC.RESULTS HCC incidence was 4.68/100PY(95%CI,3.09-6.81)in the DAAs treatment group,while it was 3.00/100PY(95%CI,1.50-5.37)in the non-antiviral treatment group,and the relative risk was 1.82(95%CI,0.93-3.53,P>0.05).The incidence of HCC at 12,24,36 and 48 months was 3.39%,6.36%,8.47%and 10.17%in the DAAs treatment group,and it was 0%,0%,3.39%and 9.32%in the non-antiviral treatment group,respectively.Age>58[hazard ratio(HR)=1.089;95%CI,1.033-1.147;P=0.002]and liver stiffness measurement>27.85 kPa(HR=1.043;95%CI,1.022-1.065;P=0.000)were risk factors for HCC in all patients(n=427),and DAAs treatment didn’t show protective efficacy.CONCLUSION DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months,and even increased the incidence of HCC in 36 months.

关键词： Direct-acting antivirals Sustained viral response Cirrhosis Hepatocellular carcinoma Risk factor

Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141,DDHD2,and LHFPL5

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Frontiers of Medicine 2024年第1期18卷 81-97页

作者： Liwei Sun xueting Yang Amjad Khan xue Yu han Zhang Shirui han Xiaerbati Habulieti Yang Sun Rongrong Wang xue Zhang McKusick-Zhang Center for Genetic Medicine State Key Laboratory for Complex Severe and Rare DiseasesInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing100005China Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive MedicineNational Key Clinical Speciality Construction Project(Obstetrics and Gynecology)Chongqing Health Center for Women and ChildrenChongqing400013China Chongqing Clinical Research Center for Reproductive Medicine Women and Children’s Hospital of Chongqing Medical UniversityChongqing400013China Faculty of Biological Sciences Department of ZoologyUniversity of Lakki MarwatKhyber Pakhtunkhwa28420Pakistan Institute for Medical Genetics and Applied Genomics University of TübingenTübingen72076Germany Alexander von Humboldt fellowship Foundation Berlin10117Germany Department of Pediatrics The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Department of Laboratory Medicine State Key Laboratory for Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China

Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder autosomal recessive intellectual disability consanguinity spastic paraplegia hearing loss TMEM141

Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation

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Biomedical and Environmental Sciences 2024年第4期37卷 354-366页

作者： mei Peng DING En Min YIN Hao Yang DING xue xue WANG Huan WANG Jian Feng han Lei ZhanG Heng Dong ZHU Bao Li School of Public Health Nanjing Medical UniversityNanjing 210000JiangsuChina Institute of Occupational Disease Prevention Jiangsu Province Center for Disease Prevention and ControlNanjing 21000JiangsuChina Suzhou Center for Disease Prevention and Control Suzhou 215004JiangsuChina Center for Global Health School of Public HealthNanjing Medical UniversityNanjing 210000JiangsuChina

Objective This study investigated the impact of occupational mercury(Hg) exposure on human gene transcription and expression, and its potential biological mechanisms.Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN lowexpression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA.Results Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model(25 and 10 μmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression.Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels.Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

关键词： PTEN Occupational mercury exposure Occupational health PI3K/AKT pathway 293T cell IL-6

Variability of the Pacific subtropical cells under global warming in CMIP6 models

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Journal of Oceanology and Limnology 2024年第1期42卷 24-40页

作者： xue han Junqiao FENG Yunlong LU Dunxin HU Key Laboratory of Ocean Circulation and Waves Chinese Academy of SciencesQingdao 266071China Institute of Oceanology Chinese Academy of SciencesQingdao 266071China University of Chinese Academy of Sciences Beijing 100049China Center for Ocean Mega-Science Chinese Academy of SciencesQingdao 266071China Laboratory for Ocean Dynamics and Climate Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China

The Pacific subtropical cells(STCs)are shallow meridional overturning circulations connecting the tropics and subtropics,and are assumed to be an important driver of the tropical Pacific decadal variability.The variability of STCs under global warming is investigated using multimodal outputs from the latest phase of the Coupled Model Inter-comparison Project(CMIP6)and ocean reanalysis products.Firstly,the volume transport diagnostic analysis is employed to evaluate how coupled models and ocean reanalysis products reproduce interior STC transport.The variation of heat transport by the interior STC under the high-emissions warming scenarios is also analyzed.The results show that the multimodal-mean linear trends of the interior STC transport along 9°S and 9°N are-0.02 Sv/a and 0.04 Sv/a under global warming,respectively,which is mainly due to the combined effect of the strengthened upper oceanic stratification and the weakening of wind field.There is a compensation relationship between the interior STC and the western boundary transport in the future climate,and the compensation relationship of 9°S is more significant than that of 9°N.In addition,compared with ocean reanalysis products,the coupled models tend to underestimate the variability of the interior STC transport convergence,and thus may lose some sea surface temperature(SST)driving force,which may be the reason for the low STC-SST correlation simulated by the model.The future scenario simulation shows that the heat transport of interior STC is weakened under global warming,with a general agreement across models.

关键词： interior subtropical cell(STC) global warming Coupled Model Inter-comparison Project(CMIP6) western boundary transport

Effects of iron oxide on crystallization behavior and spatial distribution of spinel in stainless steel slag

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International Journal of Minerals,Metallurgy and Materials 2024年第2期31卷 292-300页

作者： Zihang Yan Qing Zhao Chengzhi han Xiaohui mei Chengjun Liu Maofa Jiang Key Laboratory for Ecological Metallurgy of Multimetallic Mineral(Ministry of Education Northeastern UniversityShenyang 110819China School of Metallurgy Northeastern UniversityShenyang 110819China

Chromium plays a vital role in stainless steel due to its ability to improve the corrosion resistance of the latter.However,the re-lease of chromium from stainless steel slag(SSS)during SSS stockpiling causes detrimental environmental issues.To prevent chromium pollution,the effects of iron oxide on crystallization behavior and spatial distribution of spinel were investigated in this work.The results revealed that FeO was more conducive to the growth of spinels compared with Fe2O3 and Fe3O4.Spinels were found to be mainly distrib-uted at the top and bottom of slag.The amount of spinel phase at the bottom decreased with the increasing FeO content,while that at the top increased.The average particle size of spinel in the slag with 18wt%FeO content was 12.8μm.Meanwhile,no notable structural changes were observed with a further increase in FeO content.In other words,the spatial distribution of spinel changed when the content of iron oxide varied in the range of 8wt%to 18wt%.Finally,less spinel was found at the bottom of slag with a FeO content of 23wt%.

关键词： stainless steel slag spinel chromium waste remediation ferrous oxide

Effect of intubation in patients with functional epiphora after endoscopic dacryocystorhinostomy

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International Journal of Ophthalmology(English edition) 2023年第7期16卷 1060-1064页

作者： xue-mei han Wen-Hao Jiang Wen-Can Wu Bo Yu Department of Ophthalmology the First Affiliated Hospital of Zhejiang Chinese Medicine UniversityHangzhou 310000Zhejiang ProvinceChina Department of Ophthalmology the Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000Zhejiang ProvinceChina Department of Orbital and Oculoplastic Surgery National Clinical Research Center for Ocular DiseasesEye HospitalWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina

AIM:To investigate the effect of bicanalicular silicone tube intubation(BSTI)in the treatment of functional epiphora after endoscopic dacryocystorhinostomy(En-DCR).METHODS:Clinical data of 84 patients(95 eyes)with functional epiphora after En-DCR were retrospectively analyzed.Functional epiphora was confirmed as persistent or recurrent epiphora by fluorescein dye disappearance test(FDDT),lacrimal irrigation test,as well as endoscopic examination.Secondary BSTIs were recommended for patients with functional epiphora.These tubes were removed 1mo after surgery.Functional success and associated complications were assessed after 2y of follow-up.RESULTS:Seven patients(9 eyes)refused intervention,5 patients(6 eyes)did not complete postoperative followup,and 1 patient(1 eye)developed tube prolapse within 1mo after surgery.Seventy-one patients(79 eyes)were included at last.Functional success ratios at six months,one year,as well as two years post-operation were 94.9%(75/79),92.4%(73/79),and 91.1%(72/79),respectively.Three eyes presented with punctal slitting(2 eyes without epiphora),1 eye with proximal canaliculus slitting,1 eye with canaliculus stenosis and 4 eyes with still present functional epiphora without detectable abnormal at the last follow-up.CONCLUSION:Secondary intubation is an effective procedure with low recurrence probability for functional epiphora after En-DCR.Punctal and canaliculus injury are the main tube-associated complications after secondary intubation.

关键词： bicanalicular silicone tube endoscopic dacryocystorhinostomy functional epiphora

Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

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Biomedical and Environmental Sciences 2024年第1期37卷 85-95页

作者： WANG han Lin xue Yan Feng CUI Bao Qiu LIU Hong SHEN Xin Xin Shandong Provincial Research Center for Bioinformatic Engineering and Technique School of Life SciencesShandong University of TechnologyZibo 255049ShandongChina Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013ShanxiChina State Key Laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

关键词： Risk factors Drug targets Depression Major depressive disorder Two-sample Mendelian randomization